SEX-SPECIFIC MODIFIERS OF TAIL DEVELOPMENT IN MICE HETEROZYGOUS FOR THE BRACHYURY (T) MUTATION

The brachyury, or T, locus encodes a transcription factor that plays a crucial role in the early development of all animals. In the mouse, a nimals heterozygous for a null mutation at this locus are born with a characteristic short tail. Expressivity of the short tail phenotype is greatly affected by genetic background. As a genetic entry into the i dentification of genes that interact with the Brachyury locus, we have performed a QTL analysis for modifiers of this phenotype. Surprisingl y, we discovered that the major modifiers uncovered all act in a sex-l imited manner. We have identified two QTLs-Brml on Chr 9 and Brm2 on C hr 15-that act only in female offspring(N-2) from female T/+ parents ( F-1) and are responsible together for most, or all, of the genetic var iance in phenotypic expression observed between C57BL/10 and C3H/HeJ a nimals.